Cue-Evoked Dopamine Promotes Conditioned Responding during Learning

Neuron. 2020 Apr 8;106(1):142-153.e7. doi: 10.1016/j.neuron.2020.01.012. Epub 2020 Feb 5.


Dopamine neurons mediate the association of conditioned stimuli (CS) with reward (unconditioned stimuli, US) by signaling the discrepancy between predicted and actual reward during the US. Some theoretical models suggest that learning is also influenced by the salience or associability of the CS. A hallmark of CS associability models is that they can explain latent inhibition, i.e., the observation that novel CS are more effectively learned than familiar CS. Novel CS are known to activate dopamine neurons, but whether those responses affect associative learning has not been investigated. Here, we used fiber photometry to characterize dopamine responses to inconsequential familiar and novel stimuli. Using bidirectional optogenetic modulation during conditioning, we then show that CS-evoked dopamine promotes conditioned responses. This suggests that Pavlovian conditioning is influenced by CS dopamine, in addition to US reward prediction errors. Accordingly, the absence of dopamine responses to familiar CS might explain their slower learning in latent inhibition.

Keywords: associative learning; cue associability; dopamine; latent inhibition; stimulus familiarity; stimulus novelty.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Association Learning / physiology*
  • Conditioning, Classical / physiology*
  • Cues
  • Dopamine / metabolism*
  • Dopaminergic Neurons / metabolism
  • Dopaminergic Neurons / physiology*
  • Learning
  • Mice
  • Optogenetics
  • Pars Compacta / diagnostic imaging
  • Pars Compacta / metabolism*
  • Photometry
  • Prefrontal Cortex
  • Presynaptic Terminals
  • Recognition, Psychology
  • Reward*
  • Ventral Tegmental Area / diagnostic imaging
  • Ventral Tegmental Area / metabolism*


  • Dopamine